title: Environmentally persistent free radicals decrease cardiac function before and after ischemia/reperfusion injury in vivo.
abstract: Exposure to airborne particles is associated with increased cardiovascular morbidity and mortality. During the combustion of chlorine-containing hazardous materials and fuels, chlorinated hydrocarbons chemisorb to the surface of transition metal-oxide-containing particles, reduce the metal, and form an organic free radical. These radical-particle systems can survive in the environment for days and are called environmentally persistent free radicals (EPFRs). This study determined whether EPFRs could decrease left ventricular function before and after ischemia and reperfusion (I/R) in vivo. Male Brown-Norway rats were dosed (8 mg/kg, intratracheal) 24 h prior to testing with particles containing the EPFR of 1, 2-dichlorobenzene (DCB230). DCB230 treatment decreased systolic and diastolic function. DCB230 also produced pulmonary and cardiac inflammation. After ischemia, systolic, but not diastolic function was significantly decreased in DCB230-treated rats. Ventricular function was not affected by I/R in control rats. There was greater oxidative stress in the heart and increased 8-isoprostane (biomarker of oxidative stress) in the plasma of treated vs. control rats after I/R. These data demonstrate for the first time that DCB230 can produce inflammation and significantly decrease cardiac function at baseline and after I/R in vivo. Furthermore, these data suggest that EPFRs may be a risk factor for cardiac toxicity in healthy individuals and individuals with ischemic heart disease. Potential mechanisms involving cytokines/chemokines and/or oxidative stress are discussed.
authors.affiliation: Department of Cardiopulmonary Sciences, LSU Health Sciences Center, New Orleans, LA 70112, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Lord
authors.forename: David
authors.initials: D
authors.lastname: Moll
authors.forename: John K
authors.initials: JK
authors.lastname: Lindsey
authors.forename: Sarah
authors.initials: S
authors.lastname: Mahne
authors.forename: Girija
authors.initials: G
authors.lastname: Raman
authors.forename: Tammy
authors.initials: T
authors.lastname: Dugas
authors.forename: Stephania
authors.initials: S
authors.lastname: Cormier
authors.forename: Dana
authors.initials: D
authors.lastname: Troxlair
authors.forename: Slawo
authors.initials: S
authors.lastname: Lomnicki
authors.forename: Barry
authors.initials: B
authors.lastname: Dellinger
authors.forename: Kurt
authors.initials: K
authors.lastname: Varner
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D016207:Cytokines / Q000378:metabolism; D004777:Environment; D005609:Free Radicals / Q000633:toxicity*; D005786:Gene Expression Regulation / Q000187:drug effects; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology*; D006334:Heart Function Tests / Q000187:drug effects*; D006352:Heart Ventricles / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000503:physiopathology*; D018384:Oxidative Stress / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011914:Rats, Inbred BN; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D016207:Cytokines; D005609:Free Radicals; D012333:RNA, Messenger